Publications

Arrays of high-aspect-ratio (HAR) nano- and microstructures are of great interest for designing surfaces for applications in optics, bio−nano interfaces, microelectromechanical systems, and microfluidics, but the difficulty of systematically and conveniently varying the geometries of these structures significantly limits their design and optimization for a specific function. This paper demonstrates a low-cost, high-throughput benchtop method that enables a HAR array to be reshaped with nanoscale precision by electrodeposition of conductive polymers. The method—named STEPS (structural transformation by electrodeposition on patterned substrates)—makes it possible to create patterns with proportionally increasing size of original features, to convert isolated HAR features into a closed-cell substrate with a continuous HAR wall, and to transform a simple parent two-dimensional HAR array into new three-dimensional patterned structures with tapered, tilted, anisotropic, or overhanging geometries by controlling the deposition conditions. We demonstrate the fabrication of substrates with continuous or discrete gradients of nanostructure features, as well as libraries of various patterns, starting from a single master structure. By providing exemplary applications in plasmonics, bacterial patterning, and formation of mechanically reinforced structures, we show that STEPS enables a wide range of studies of the effect of substrate topography on surface properties leading to optimization of the structures for a specific application. This research identifies solution-based deposition of conductive polymers as a new tool in nanofabrication and allows access to 3D architectures that were previously difficult to fabricate.

Die Körpergröße ist weitgehend genetisch festgelegt, dennoch beobachtet man in den vergangenen Jahrzehnten weltweit eine stete Zunahme bei Kindern und Erwachsenen: Die Kinder sind im Erwachsenenalter fast immer deutlich größer als ihre Eltern. Die größte Zunahme der Körpergröße über die letzten Jahrzehnte findet man in den Niederlanden. Holländische Männer sind mittlerweile 20 cm größer als sie es vor 150 Jahren waren. Interessanterweise ist in den Niederlanden auch der Pro-Kopf-Konsum von Milch und Milchprodukten weltweit am höchsten.

Abstract The purpose of our study was to examine the long-term within-person reproducibility of bisphenol A (BPA) and 8 phthalate metabolites. Associations of BPA and phthalates with health are increasingly being investigated in epidemiologic studies, although existing studies are largely cross-sectional. Most previous studies of within-person variability in urinary BPA and phthalate metabolite concentrations have focused on stability over 3 months or less. Long-term reproducibility data are needed to assess the potential usefulness of these biomarkers for predicting risk of disease onset in prospective studies. We measured BPA and 8 phthalate metabolites in spot urine samples donated 1 to 3 years apart by women in the Nurses' Health Study and Nurses' Health Study II (n=80 for analyses of BPA; n=40 for phthalate metabolites); 86% of samples were first-morning urines. Specific phthalate metabolites were mono-ethyl phthalate (MEP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), mono-benzyl phthalate (MBzP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-hydrohexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-(2-ethyl-5carboxypentyl) phthalate (MECPP). To measure within-person reproducibility, we calculated Spearman rank correlation coefficients and intraclass correlations (ICCs) for creatinine-adjusted BPA and phthalate metabolite concentrations; ICCs were estimated using natural log-transformed values. Additional analyses were restricted to first-morning urine samples. Distributions (medians [5th to 95th percentiles]) of creatinine-adjusted analyte concentrations (ng/mg creatinine) were: 3 (1-6) for BPA, 141 (21-895) for MEP, 4 (1-12) for MiBP, 37 (10-177) for MnBP, 14 (4-97) for MBzP, 5 (2-26) for MEHP, 32 (9-163) for MEHHP, 26 (7-136) for MEOHP, and 43 (16-215) for MECPP. Over 1 to 3 years, within-person variability of BPA was high relative to total variability (ICC=0.14) and rankings of BPA levels between time-points were weakly correlated (Spearman correlation=0.19). All phthalate metabolites, except MEHP, demonstrated moderate within-person stability over time (Spearman correlation or ICC=0.39-0.55). Restricting analyses to first-morning urine samples did not alter results. Overall, we found that single measurements of BPA in spot urine samples were highly variable within women over 1 to 3 years. However, the majority of urinary phthalate metabolites appeared moderately reproducible within women over time. Our results suggest that investigation of associations between a single urinary BPA measurement and disease risk likely will be challenging in epidemiologic studies, while single measurements of urinary phthalate metabolites are reasonable measures of long-term exposure. Further, reproducibility data could be used to correct for within-person variability that results in the attenuation of estimates of relative risk. Citation Format: Mary Townsend, Adrian Franke, Xingnan Li, Frank Hu, A. Heather Eliassen. Within-person reproducibility of urinary bisphenol A and phthalate metabolites among women in the Nurses' Health Studies. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr 35.

We study the buckling of hemispherical elastic shells subjected to the combined effect of pressure loading and a probing force. We perform an experimental investigation using thin shells of nearly uniform thickness that are fabricated with a well-controlled geometric imperfection. By systematically varying the indentation displacement and the geometry of the probe, we study the effect that the probe-induced deflections have on the buckling strength of our spherical shells. The experimental results are then compared to finite element simulations, as well as to recent theoretical predictions from the literature. Inspired by a nondestructive technique that was recently proposed to evaluate the stability of elastic shells, we characterize the nonlinear load-deflection mechanical response of the probe for different values of the pressure loading. We demonstrate that this nondestructive method is a successful local way to assess the stability of spherical shells.

Abstract Background Women with gestational diabetes mellitus (GDM) may be at an increased risk of liver complications because chronic hyperglycemia is a risk factor for liver fat accumulation and potential liver dysfunction. Large prospective studies examining liver fat accumulation following a GDM pregnancy are lacking. Methods The Diabetes & Women's Health Study (2012‐2014) examined the association between GDM and subsequent fatty liver scores among 607 women with and 619 women without GDM in the Danish National Birth Cohort. Nine to 16 years postpartum, a clinical examination was performed, with measurement of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ‐glutamyl transferase, from which fatty liver scoring indices were calculated to assess liver fat score, fatty liver index, hepatic steatosis index, and liver fat percentage. Relative risks (RR) with 95% confidence intervals (CI) for elevated liver scoring indices by GDM status were assessed adjusting for major risk factors, including prepregnancy body mass index. Results Women with prior GDM had higher adjusted ALT and AST levels than women without GDM (by 6.7% [95% CI 1.7‐12.0] and 4.8% [95% CI 0.6‐9.1], respectively). Women with GDM also had adjusted increased risks for elevated liver fat score (RR 2.34; 95% CI 1.68‐3.27), fatty liver index (RR 1.59; 95% CI 1.27‐1.99), and hepatic steatosis index (RR 1.44; 95% CI 1.21‐1.71). Conclusions Women with GDM during pregnancy were at an increased risk for fatty liver 9 to 16 years postpartum. Gestational diabetes mellitus may serve as another risk indicator for the early identification and prevention of liver fat accumulation.

Abstract Painful temporomandibular disorders (TMDs) are the leading cause of chronic orofacial pain, but its underlying molecular mechanisms remain obscure. Although many environmental factors have been associated with higher risk of developing painful TMD, family and twin studies support a heritable genetic component as well. We performed a genome-wide association study assuming an additive genetic model of TMD in a discovery cohort of 999 cases and 2031 TMD-free controls from the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study. Using logistic models adjusted for sex, age, enrollment site, and race, we identified 3 distinct loci that were significant in combined or sex-segregated analyses. A single-nucleotide polymorphism on chromosome 3 (rs13078961) was significantly associated with TMD in males only (odds ratio = 2.9, 95% confidence interval: 2.02-4.27, P = 2.2 × 10 −8 ). This association was nominally replicated in a meta-analysis of 7 independent orofacial pain cohorts including 160,194 participants (odds ratio = 1.16, 95% confidence interval: 1.0-1.35, P = 2.3 × 10 −2 ). Functional analysis in human dorsal root ganglia and blood indicated this variant is an expression quantitative trait locus, with the minor allele associated with decreased expression of the nearby muscle RAS oncogene homolog ( MRAS ) gene (beta = −0.51, P = 2.43 × 10 −5 ). Male mice, but not female mice, with a null mutation of Mras displayed persistent mechanical allodynia in a model of inflammatory pain. Genetic and behavioral evidence support a novel mechanism by which genetically determined MRAS expression moderates the resiliency to chronic pain. This effect is male-specific and may contribute to the lower rates of painful TMD in men.

This work describes the development of an integrated analytical system that enables high-throughput density measurements of diamagnetic particles (including cells) using magnetic levitation (MagLev), 96-well plates, and a flatbed scanner. MagLev is a simple and useful technique with which to carry out density-based analysis and separation of a broad range of diamagnetic materials with different physical forms (e.g., liquids, solids, gels, pastes, gums, etc.); one major limitation, however, is the capacity to perform high-throughput density measurements. This work addresses this limitation by (i) re-engineering the shape of the magnetic fields so that the MagLev system is compatible with 96-well plates, and (ii) integrating a flatbed scanner (and simple optical components) to carry out imaging of the samples that levitate in the system. The resulting system is compatible with both biological samples (human erythrocytes) and nonbiological samples (simple liquids and solids, such as 3-chlorotoluene, cholesterol crystals, glass beads, copper powder, and polymer beads). The high-throughput capacity of this integrated MagLev system will enable new applications in chemistry (e.g., analysis and separation of materials) and biochemistry (e.g., cellular responses under environmental stresses) in a simple and label-free format on the basis of a universal property of all matter, i.e., density.